Atmospheric Secondary Inorganic Particulate Matter: The Toxicological Perspective as a Basis for Health Effects Risk Assessment

Epidemiological studies have provided evidence for an association between exposure to ambient particulate matter and increased mortality and morbidity. However, the exact physicochemical nature of the responsible components is not as yet clear. One major constituent of the ambient aerosol is secondary inorganic particles, which are produced within the atmosphere via chemical reactions and are dominated by sulfates and nitrates. This article reviews the biological effects resulting from exposure to these ambient aerosol constituents. It was developed based upon available data from peer reviewed published papers as well as publicly available reports on controlled animal and human clinical exposure studies. The aim was to provide a toxicological basis for addressing the issue of whether ambient concentrations of these secondary aerosols in two venues, namely the United States and the Netherlands, could be causally related to reported human health effects associated with exposure to ambient particulate matter. Evaluation of the toxicological database suggests that these particles have little biological potency in normal humans or animals, or in the limited compromised animal models studied at environmentally relevant levels. There are, however, some critical caveats in this analysis that must be considered. First, it is important to understand the relationship between animal exposure studies and actual human exposures, in terms of both particle size and inhaled dose. Second, it is necessary to consider the physicochemical characteristics of the chemical species within ambient air compared to the characteristics of those used in controlled studies. Third, there is the issue of relevance of the exposure models used in these studies to those populations that may be affected by exposure to ambient particulates. Finally, the potential for interactions between particulates and ambient gases in the total atmospheric mix must be considered in developing conclusions as to exposure concentrations for the former constituents of polluted air that may be hazardous to public health.

[1]  D. Menzel,et al.  Ammonium and sulfate ion release of histamine from lung fragments. , 1975, Archives of environmental health.

[2]  J. Balmes,et al.  Lack of bronchoconstrictor response to sulfuric acid aerosols and fogs. , 1991, The American review of respiratory disease.

[3]  M. Newhouse,et al.  Effect of TLV levels of SO2 and H2 SO4 on bronchial clearance in exercising man. , 1978, Archives of environmental health.

[4]  P. Morrow,et al.  Sulfuric acid aerosol followed by ozone exposure in healthy and asthmatic subjects. , 1995, Environmental research.

[5]  M. Lippmann,et al.  Effects of submicrometer sulfuric acid aerosols on mucociliary transport and respiratory mechanics in asymptomatic asthmatics. , 1985, Environmental research.

[6]  P. Drinker,et al.  Toxicity of sulfuric acid mist to guinea pigs. , 1952, A.M.A. archives of industrial hygiene and occupational medicine.

[7]  Regional Variations in Sulfate and Nitrate on Annual, Seasonal, and Synoptic Time Scales , 2001, Journal of the Air & Waste Management Association.

[8]  P. Kinney,et al.  Long-term intermittent exposure to sulfuric acid aerosol, ozone, and their combination: alterations in tracheobronchial mucociliary clearance and epithelial secretory cells. , 1992, Experimental lung research.

[9]  C. Kim,et al.  Effects of nitric acid on carbachol reactivity of the airways in normal and allergic sheep. , 1982, Archives of environmental health.

[10]  M. Lippmann,et al.  Toxicological bases for the setting of health-related air pollution standards. , 2000, Annual review of public health.

[11]  B. Laube,et al.  Acute exposure to acid fog. Effects on mucociliary clearance. , 1993, The American review of respiratory disease.

[12]  P. Morrow,et al.  Effects of Inhaled Acid Aerosols on Respiratory Function: The Role of Endogenous Ammonia , 1989 .

[13]  M. Lippmann,et al.  Effects of sulfuric acid aerosol on respiratory mechanics and mucociliary particle clearance in healthy nonsmoking adults. , 1981, American Industrial Hygiene Association journal.

[14]  R. Douglas,et al.  Development of airway reactivity to nitrates in subjects with influenza. , 1980, The American review of respiratory disease.

[15]  R. Burnett,et al.  Inhalation toxicology of urban ambient particulate matter: acute cardiovascular effects in rats. , 2001, Research report.

[16]  J. Zelikoff,et al.  EFFECTS OF INHALED SULFURIC ACID AEROSOLS ON PULMONARY IMMUNOCOMPETENCE: A COMPARATIVE STUDY IN HUMANS AND ANIMALS , 1997 .

[17]  J. Zelikoff,et al.  Pulmonary Effects of Repeated Episodic Exposures to Nitric Acid Vapor Alone and in Combination with Ozone , 1994 .

[18]  U. Epa Air Quality Criteria for Particulate Matter , 1996 .

[19]  J. Thompson,et al.  The role of titratable acidity in acid aerosol-induced bronchoconstriction. , 2015, The American review of respiratory disease.

[20]  R. Hyatt,et al.  A canine model of bronchial injury induced by nitric acid. Lung mechanics and morphologic features. , 1986, The American review of respiratory disease.

[21]  H. D. Kerr,et al.  Sulfur dioxide and ammonium sulfate effects on pulmonary function and bronchial reactivity in human subjects. , 1984, American Industrial Hygiene Association journal.

[22]  S. Greenberg,et al.  Alveolar epithelial cells following exposure to nitric acid. Electron microscopic study in rats. , 1971, Archives of environmental health.

[23]  Jack Siemiatycki,et al.  Risk Factors For Cancer In The Workplace , 1991 .

[24]  C. Jadue,et al.  Pulmonary function tests in the detection of small airway obstruction in a canine model of bronchiolitis obliterans. , 1984, The American review of respiratory disease.

[25]  J M Wolfson,et al.  Mechanisms of morbidity and mortality from exposure to ambient air particles. , 2000, Research report.

[26]  C. Franklin,et al.  Acid particles and the tracheobronchial region of the respiratory system--an "irritation-signaling" model for possible health effects. , 1987, JAPCA.

[27]  M. L. Laucks,et al.  Aerosol Technology Properties, Behavior, and Measurement of Airborne Particles , 2000 .

[28]  S. Kleeberger,et al.  Inhalation of acid coated carbon black particles impairs alveolar macrophage phagocytosis. , 1996, Toxicology letters.

[29]  B. Holma Influence of buffer capacity and pH-dependent rheological properties of respiratory mucus on health effects due to acidic pollution. , 1985, The Science of the total environment.

[30]  M. Kleinman,et al.  Chronic inhalation exposure to ozone and nitric acid elevates stress-inducible heat shock protein 70 in the rat lung. , 1996, Toxicology.

[31]  B O Stuart,et al.  Deposition and clearance of inhaled particles. , 1976, Environmental health perspectives.

[32]  R. Schlesinger,et al.  Exposure-response relationship of bronchial mucociliary clearance in rabbits following acute inhalations of sulfuric acid mist. , 1984, Toxicology letters.

[33]  D. Costa,et al.  Cardiac arrhythmia induction after exposure to residual oil fly ash particles in a rodent model of pulmonary hypertension. , 1998, Toxicological sciences : an official journal of the Society of Toxicology.

[34]  Division on Earth Risk Assessment in the Federal Government: Managing the Process , 1983 .

[35]  W G Kreyling,et al.  Health effects of sulfur-related environmental air pollution. III. Nonspecific respiratory defense capacities. , 1999, Inhalation toxicology.

[36]  F. Hahn,et al.  Influence of exposure concentration or dose on the distribution of particulate material in rat and human lungs. , 2001, Environmental health perspectives.

[37]  Fritz Haber,et al.  Zur Geschichte des Gaskrieges , 1924 .

[38]  H Schulz,et al.  Health effects of sulfur-related environmental air pollution. IV. Respiratory lung function. , 1999, Inhalation toxicology.

[39]  M. Kleinman,et al.  Inhalation of resuspended road dust, but not ammonium nitrate, decreases the expression of the pulmonary macrophage Fc receptor. , 1994, Toxicology letters.

[40]  Kazuhiko Ito,et al.  A multi-year study of air pollution and respiratory hospital admissions in three New York State metropolitan areas: results for 1988 and 1989 summers. , 1992, Journal of exposure analysis and environmental epidemiology.

[41]  J. Gearhart,et al.  Response of the tracheobronchial mucociliary clearance system to repeated irritant exposure: effect of sulfuric acid mist on function and structure. , 1988, Experimental lung research.

[42]  J. Koenig,et al.  The effects of inhaled sulfuric acid on pulmonary function in adolescent asthmatics. , 1983, The American review of respiratory disease.

[43]  M. Kleinman,et al.  Effect of Nitric Acid Vapor on the Response to Inhaled Ozone , 1992 .

[44]  J. Gearhart,et al.  Early alveolar clearance in rabbits intermittently exposed to sulfuric acid mist. , 1986, Journal of toxicology and environmental health.

[45]  W. Pierson,et al.  Effects of inhalation of acidic compounds on pulmonary function in allergic adolescent subjects. , 1989, Environmental health perspectives.

[46]  K. T. Whitby,et al.  Measurements of aerosols produced by the photochemical oxidation of SO2 in air , 1975 .

[47]  J. Schwartz,et al.  Assessing confounding, effect modification, and thresholds in the association between ambient particles and daily deaths. , 2000, Environmental health perspectives.

[48]  Lung-Chi Chen,et al.  Number Concentration and Mass Concentration as Determinants of Biological Response to Inhaled Irritant Particles , 1995 .

[49]  D. Chang,et al.  A mechanism of synergistic lung damage by ozone and a respirable aerosol. , 1984, Experimental lung research.

[50]  R. Schlesinger,et al.  Comparative irritant potency of inhaled sulfate aerosols--effects on bronchial mucociliary clearance. , 1984, Environmental research.

[51]  W. Pierson,et al.  Coarse- and fine-particle atmospheric nitrate and HNO3(g) in Claremont, California, during the 1985 nitrogen species methods comparison study , 1988 .

[52]  J. Balmes,et al.  Effects of nitric acid gas alone or in combination with ozone on healthy volunteers. , 1993, The American review of respiratory disease.

[53]  Michelle L. Bell,et al.  A Meta-Analysis of Time-Series Studies of Ozone and Mortality With Comparison to the National Morbidity, Mortality, and Air Pollution Study , 2005, Epidemiology.

[54]  E. Avol,et al.  Effect of droplet size on respiratory responses to inhaled sulfuric acid in normal and asthmatic volunteers. , 1989, The American review of respiratory disease.

[55]  M. Sackner,et al.  Effects of sodium nitrate aerosol on cardiopulmonary function of dogs, sheep, and man. , 1979, Environmental research.

[56]  R. Phalen,et al.  Effects of sulfate aerosols in combination with ozone on elimination of tracer particles inhaled by rats. , 1980, Journal of toxicology and environmental health.

[57]  Lung-Chi Chen,et al.  Effects of fine and ultrafine sulfuric acid aerosols in guinea pigs: alterations in alveolar macrophage function and intracellular pH. , 1992, Toxicology and applied pharmacology.

[58]  K. R. Anderson,et al.  Human exposure to ferric sulfate aerosol: effects on pulmonary function and respiratory symptoms. , 1981, American Industrial Hygiene Association journal.

[59]  Bert Brunekreef,et al.  Daily Mortality and Air Pollution in the Netherlands , 2000, Journal of the Air & Waste Management Association.

[60]  M. Lippmann,et al.  Effects of short-term exposures to sulfuric acid and ammonium sulfate aerosols upon bronchial airway function in the donkey. , 1978, American Industrial Hygiene Association journal.

[61]  R. Schlesinger,et al.  Response of the bronchial mucociliary clearance system in rabbits to inhaled sulfite and sulfuric acid aerosols. , 1983, Toxicology and applied pharmacology.

[62]  Y. Zee,et al.  Studies on the enhancement of allergic lung sensitization by inhalation of ozone and sulfuric acid aerosol. , 1980, Journal of environmental pathology and toxicology.

[63]  D. Brownstein Reflex-mediated desquamation of bronchiolar epithelium in guinea pigs exposed acutely to sulfuric acid aerosol. , 1980, The American journal of pathology.

[64]  L. C. Chen,et al.  Furnace-generated acid aerosols: speciation and pulmonary effects. , 1989, Environmental health perspectives.

[65]  W. Halperin,et al.  Lung cancer mortality in workers exposed to sulfuric acid mist and other acid mists. , 1987, Journal of the National Cancer Institute.

[66]  W. Pierson,et al.  Respiratory effects of inhaled sulfuric acid on senior asthmatics and nonasthmatics. , 1993, Archives of environmental health.

[67]  A. Wexler,et al.  Growth and neutralization of sulfate aerosols in human airways. , 1996, Journal of applied physiology.

[68]  K. R. Anderson,et al.  Effects of prolonged, repeated exposure to ozone, sulfuric acid, and their combination in healthy and asthmatic volunteers. , 1994, American journal of respiratory and critical care medicine.

[69]  J. Schwartz,et al.  Daily changes in oxygen saturation and pulse rate associated with particulate air pollution and barometric pressure. , 1999, Research report.

[70]  D. Dockery,et al.  An association between air pollution and mortality in six U.S. cities. , 1993, The New England journal of medicine.

[71]  M. Kleinman,et al.  Effect of ammonium nitrate aerosol on human respiratory function and symptoms. , 1980, Environmental research.

[72]  M. Cipollaro,et al.  Epidemiologic and toxicologic evidence for chronic health effects and the underlying biologic mechanisms involved in sub-lethal exposures to acidic pollutants. , 1989, Archives of environmental health.

[73]  H. Fujimaki,et al.  Enhanced histamine release from lung mast cells of guinea pigs exposed to sulfuric acid aerosols. , 1992, Environmental research.

[74]  R. Schlesinger Interaction of gaseous and particulate pollutants in the respiratory tract: mechanisms and modulators. , 1995, Toxicology.

[75]  B. Holma Effects of inhaled acids on airway mucus and its consequences for health. , 1989, Environmental health perspectives.

[76]  Llo,et al.  Composition and Origin of Airborne Particulate Matterin the Netherlands , 2001 .

[77]  K. R. Anderson,et al.  Short-term respiratory effects of sulfuric acid in fog: a laboratory study of healthy and asthmatic volunteers. , 1988, JAPCA.

[78]  M Lippmann,et al.  Respiratory hospital admissions and summertime haze air pollution in Toronto, Ontario: consideration of the role of acid aerosols. , 1994, Environmental research.

[79]  D M Hyde,et al.  Synergistic effects on rat lungs of mixtures of oxidant air pollutants (ozone or nitrogen dioxide) and respirable aerosols. , 1983, The American review of respiratory disease.

[80]  T. Larson,et al.  Measurements of respiratory ammonia and the chemical neutralization of inhaled sulfuric acid aerosol in anesthetized dogs. , 1982, The American review of respiratory disease.

[81]  M. Lippmann,et al.  Dose-dependent effects of submicrometer sulfuric acid aerosol on particle clearance from ciliated human lung airways. , 1984, American Industrial Hygiene Association journal.

[82]  J. Haseman,et al.  Effects in rats and guinea pigs of short-term exposures to sulfuric acid mist, ozone, and their combination. , 1977, Journal of Toxicology and Environmental Health, Part A.

[83]  B Y Cockrell,et al.  Effects in rats and guinea pigs of six-month exposures to sulfuric acid mist, ozone, and their combination. , 1978, Journal of toxicology and environmental health.

[84]  K. T. Whitby THE PHYSICAL CHARACTERISTICS OF SULFUR AEROSOLS , 1978 .

[85]  R. Burnett,et al.  A time-series analysis of acidic particulate matter and daily mortality and morbidity in the Buffalo, New York, region. , 1999, Environmental health perspectives.

[86]  K. T. Knapp,et al.  The sampling of reactive atmospheric species by transition-flow reactor: application to nitrogen species , 1988 .

[87]  R. Schlesinger Factors affecting the response of lung clearance systems to acid aerosols: role of exposure concentration, exposure time, and relative acidity. , 1989, Environmental health perspectives.

[88]  P. de Vuyst,et al.  Acute exposure to realistic acid fog: effects on respiratory function and airway responsiveness in asthmatics. , 1995, Environmental research.

[89]  M. Sackner,et al.  Effects of sulfuric acid aerosol on cardiopulmonary function of dogs, sheep, and humans. , 1978, The American review of respiratory disease.

[90]  F. J. Miller Dosimetry of particles in laboratory animals and humans in relationship to issues surrounding lung overload and human health risk assessment: a critical review. , 2000, Inhalation toxicology.

[91]  J Schwartz,et al.  Air pollution and incidence of cardiac arrhythmia. , 2000, Epidemiology.

[92]  D. House,et al.  A survey of effects of gaseous and aerosol pollutants on pulmonary function of normal males. , 1983, Archives of environmental health.

[93]  P. Morrow,et al.  Airway responses to sulfate and sulfuric acid aerosols in asthmatics. An exposure-response relationship. , 1983, The American review of respiratory disease.

[94]  R. Schlesinger The interaction of inhaled toxicants with respiratory tract clearance mechanisms. , 1990, Critical reviews in toxicology.

[95]  J. Zelikoff,et al.  Modulation of pulmonary eicosanoid metabolism following exposure to sulfuric acid. , 1990, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[96]  G. T. Sanctis,et al.  Ventilatory responses in awake guinea pigs exposed to acid aerosols. , 1998, Journal of toxicology and environmental health. Part A.

[97]  R. Buschbom,et al.  Pulmonary function in elastase-treated guinea pigs and rats exposed to ammonium sulfate or ammonium nitrate aerosols. , 1985, Environmental research.

[98]  M. Sagai,et al.  Combined exposure to NO2, O3 and H2SO4-aerosol and lung tumor formation in rats. , 1992, Toxicology.

[99]  J. Schwartz,et al.  The National Morbidity, Mortality, and Air Pollution Study. Part II: Morbidity and mortality from air pollution in the United States. , 2000, Research report.

[100]  J Schwartz,et al.  Ambient pollution and heart rate variability. , 2000, Circulation.

[101]  K. R. Anderson,et al.  Human respiratory responses to an aerosol containing zinc ammonium sulfate. , 1981, Environmental research.

[102]  D V Bates,et al.  Air pollution and hospital admissions in Southern Ontario: the acid summer haze effect. , 1987, Environmental research.

[103]  D. Jacob,et al.  Chemical composition of fogwater collected along the California coast. , 1985, Environmental science & technology.

[104]  W. Pierson,et al.  Response of young asthmatic patients to inhaled sulfuric acid. , 1992, The American review of respiratory disease.

[105]  L. Friberg [Air pollution]. , 1984, Svenska lakartidningen.

[106]  J. Balmes,et al.  Acidity potentiates bronchoconstriction induced by hypoosmolar aerosols. , 1988, The American review of respiratory disease.

[107]  W G Kreyling,et al.  Health effects of sulfur-related environmental air pollution. V. Lung structure. , 1999, Inhalation toxicology.

[108]  J D Hackney,et al.  Controlled exposures of volunteers to respirable carbon and sulfuric acid aerosols. , 1992, Journal of the Air & Waste Management Association.

[109]  R. Schlesinger,et al.  Comparative biological potency of acidic sulfate aerosols: implications for the interpretation of laboratory and field studies. , 1994, Environmental research.

[110]  M. Lippmann,et al.  Effect of concentration and cumulative exposure of inhaled sulfuric acid on tracheobronchial particle clearance in healthy humans. , 1989, Environmental health perspectives.

[111]  J. Schwartz,et al.  Heart rate variability associated with particulate air pollution. , 1999, American heart journal.

[112]  R M Harrison,et al.  Particulate matter in the atmosphere: which particle properties are important for its effects on health? , 2000, The Science of the total environment.

[113]  J. Last,et al.  Synergistic interaction between nitrogen dioxide and respirable aerosols of sulfuric acid or sodium chloride on rat lungs. , 1987, Toxicology and applied pharmacology.

[114]  J. Zelikoff,et al.  Modulation of pulmonary immune defense mechanisms by sulfuric acid: effects on macrophage-derived tumor necrosis factor and superoxide. , 1992, Toxicology.

[115]  N. Roberts,et al.  Sulfuric acid aerosol exposure in humans assessed by bronchoalveolar lavage. , 1992, The American review of respiratory disease.

[116]  R. Burnett,et al.  Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. , 2002, JAMA.

[117]  J. Mauderly,et al.  Effects of sulfuric acid and nitrogen dioxide on airway responsiveness of the guinea pig. , 1981, Journal of toxicology and environmental health.

[118]  M. Cohen,et al.  Immunotoxicity of sulfuric acid aerosol: effects on pulmonary macrophage effector and functional activities critical for maintaining host resistance against infectious diseases. , 1994, Toxicology.

[119]  Bahman Asgharian,et al.  DOSIMETRIC ISSUES RELATING TO PARTICULATE TOXICITY , 1995 .

[120]  R. D. Morris,et al.  Air pollution and hospital admissions for cardiovascular disease in Detroit, Michigan. , 1995, American journal of epidemiology.

[121]  J. Koenig,et al.  Calculation of Acid Aerosol Dose , 1993 .

[122]  Brownstein Dg Reflex-mediated desquamation of bronchiolar epithelium in guinea pigs exposed acutely to sulfuric acid aerosol. , 1980 .

[123]  P. Koutrakis,et al.  Spatial variation in particulate concentrations within metropolitan Philadelphia , 1996 .

[124]  Air pollution and health: correlation or causality? The case of the relationship between exposure to particles and cardiopulmonary mortality. , 2001, Journal of the Air & Waste Management Association.

[125]  L. Bree,et al.  PULMONARY EFFECTS OF ULTRAFINE AND FINE AMMONIUM SALTS AEROSOLS IN HEALTHY AND MONOCROTALINE-TREATED RATS FOLLOWING SHORT-TERM EXPOSURE , 2002, Inhalation toxicology.

[126]  R. H. Gray,et al.  Effects of sulfuric acid mist inhalation on mucous clearance and on airway fluids of rats and guinea pigs. , 1986, Journal of toxicology and environmental health.

[127]  M. Kleinman,et al.  Controlled exposures of human volunteers to sulfate aerosols. Health effects and aerosol characterization. , 1979, The American review of respiratory disease.

[128]  E. Avol,et al.  Respiratory Dose-Response Study of Normal and Asthmatic Volunteers Exposed to Sulfuric Acid Aerosol in the Sub-Micrometer Size Range , 1988, Toxicology and industrial health.

[129]  J. Zelikoff,et al.  Comparative potency of inhaled acidic sulfates: speciation and the role of hydrogen ion. , 1990, Environmental research.

[130]  Holger Schulz,et al.  Early Response of the Canine Respiratory Tract Following Long-Term Exposure to a Sulfur(IV) Aerosol at Low Concentration. I. Rationale, Design, Methodology, and Summary , 1992 .

[131]  D. Dockery,et al.  Particulate air pollution as a predictor of mortality in a prospective study of U.S. adults. , 1995, American journal of respiratory and critical care medicine.

[132]  P. Morrow,et al.  Airway reactivity to nitrates in normal and mild asthmatic subjects. , 1979, Journal of applied physiology: respiratory, environmental and exercise physiology.

[133]  T. Larson,et al.  The chemical neutralization of inhaled sulfuric acid aerosol. , 1980, American journal of industrial medicine.

[134]  R. Busch,et al.  Experimental pulmonary emphysema induced in the rat by intratracheally administered elastase: morphogenesis. , 1984, Environmental research.

[135]  J Pekkanen,et al.  Number concentration and size of particles in urban air: effects on spirometric lung function in adult asthmatic subjects. , 2001, Environmental health perspectives.

[136]  R. Ehrlich Interaction between environmental pollutants and respiratory infections. , 1980, Environmental health perspectives.

[137]  T. Kobayashi,et al.  Effects of exposure to sulfuric acid-aerosol on airway responsiveness in guinea pigs: concentration and time dependency. , 1993, Journal of toxicology and environmental health.

[138]  M. Imai,et al.  Effects of exposure to sulfate aerosols and antigen on breathing curve patterns of guinea pigs. , 1991, Journal of toxicology and environmental health.

[139]  R. Schlesinger Effects of inhaled acids on respiratory tract defense mechanisms. , 1985, Environmental health perspectives.

[140]  Bree L van,et al.  Toxicity of Ambient Particulate Matter II. Acutetoxicity study in asthmatic mice following 3-day exposure to fine ammonium ferrosulfate, a model compound for secondaryaerosol of PM10 , 1998 .

[141]  P J Catalano,et al.  Gaseous pollutants in particulate matter epidemiology: confounders or surrogates? , 2001, Environmental health perspectives.

[142]  P. Morrow,et al.  Latent development of airway hyperreactivity in human subjects after sulfuric acid aerosol exposure , 1983 .

[143]  R. Schlesinger Exposure-Response Pattern for Sulfuric Acid-Induced Effects on Particle Clearance from the Respiratory Region of Rabbit Lungs , 1990 .